The development of an analytical procedure for lead and sulfur isotope analysis by secondary ion microprobe mass spectrometry allowed us to provide in situ isotopic microanalyses of galena crystals.We performed analyses across the growth zones of two crystals of galena from Mississippi Valley-type ore deposits, with a spatial resolution of 50 mu m and a spacing of 250 mu m. These analyses show frequent variations for both lead and sulfur isotope compositions which occurred during the time of the crystal growth. We can demonstrate that, for both elements, these variations involved changes in the sources of the brines which formed the ore deposits. The comparison of lead and sulfur isotope behavior suggests that for the Picher deposit lead and sulfur originated from common sources, whereas for the Buick mine deposit lead and sulfur had separate sources.The two galenas exhibit rapid and frequent changes in isotopic composition; this suggests numerous and discontinuous inputs of lead and sulfur to the ore deposits. This model agrees well with a physical model for Mississippi Valley-type deposits proposed by Cathles and Smith (1983). The isotopically different sources were probably different sedimentary layers and perhaps basement rocks in the same basin, whose formation waters were channeled in preferred water conduits to the ore deposit location during the subsidence of the basin, allowing mixing between the different sources to occur during the brines' travel.