A regional whole-rock oxygen isotope survey carried out in the Noranda district shows how oxygen isotope alteration can be used to guide exploration for massive sulfide deposits. The survey is based on 588 outcrop whole-rock oxygen isotope determinations from 478 sites in a approximately 35- by 50-km area between the Destor-Porcupine and Cadillac-Larder Lake breaks from east of the Horne mine to west of the Magusi River mine. The mean isotopic composition of all samples is 7.4 + or - 2 per mil (SMOW). Nested analysis of variance of 478 isotopic determinations from 371 of these sites shows that 74 percent of the total variance in whole-rock delta 18 O r (r = whole rock) is associated with outcrop location, 21 percent with outcrop sampling, and 5 percent with sample analysis. An analysis of 259 determinations indicates that rock type is statistically no more important than outcrop sampling. The statistical analysis indicates that isotopic variations greater than + or -1 per mil can be used to map the hydrothermal circulation responsible for massive sulfide mineralization. Specific traverses visually confirm the lack of 18 O dependence on rock type and the utility of a 2 per mil interpretive band. The large-scale pattern of isotopic alteration in the Noranda district is dominated by a nearly continuous 2- to 3-km-wide annulus at the margins of the Flavrian pluton of delta 18 O r < 6 per mil (with values as low as 0.6ppm). Six fingers of delta 18 O r < 6 per mil radiate from the annulus. Five of the six point up section toward most of the massive sulfide deposits in the district, including two hosted by cycle IV (Dufault granodiorite-related) extrusions. The Flavrian 18 O r depletion is surrounded up section by a approximately 10-km-wide band of patchy but intense 18 O enrichment (8.5-14ppm). The combined pattern of concentric light and heavy alteration has a diameter of approximately 30 km. The Clericy intrusion shows a similar pattern of isotope alteration on a smaller (10 km diam) scale. The Lake Dufault pluton seems to have been isotopically altered by continuing convection driven by the Flavrian hydrothermal system. Modeling suggests that the 18 O depletion is produced by water circulating toward and along the edges of an intrusion, and that the surrounding heavy alteration is produced either by seawater recharge or limited hydrothermal discharge. The large scale and coherency of the alteration pattern centered on the Flavrian pluton is remarkable and indicates that this pluton drove a major, long-lived ( approximately 10 m.y.) hydrothermal system in which convection penetrated to an >8-kin depth. The intensity and coherency of the 18 O depletion correlates with the tonnage of associated massive sulfide mineralization. Oxygen isotope depletion may in general mark the margins of plutons that have driven sufficient hydrothermal circulation to produce economic massive sulfide deposits up section. It may be possible to screen plutons for up-section massive sulfide exploration potential by collecting and isotopically analyzing approximately 50 samples from five traverses across a pluton's margins. Additional samples may provide details (light fingers) that guide exploration to particular deposits.