Supernatant fluids were prepared from human platelets (2-2.5 X 10(10)/ml) after sonication of stimulation with cross-linked IgG; together with plasma samples from two patients with different types of pemphigus, they enhanced acantholysis in cultured punch biopsy specimens of human skin. In the absence of pemphigus plasma the platelet-derived materials did not induce acantholysis. The acantholysis-enhancing effect persisted after exhaustive dialysis or heating (56 degrees C, 30 min). The platelet-derived materials did not contain plasminogen activator; plasminogen itself was detectable by zymographic analysis, although in quantities too low (0.2-0.5 micrograms/ml) to account for the acantholysis-enhancing activity. We conclude that the platelet could contribute to the pathogenesis of pemphigus. The nature of the platelet-derived acantholysis-enhancing factors is presently unknown.