Chediak-Higashi (CH) syndrome, a genetic disease affecting man and other animals, is partially characterized by defective platelets that lack serotonin and dense bodies and by impaired leukocyte function where chemotaxis, degranulation, and bacterial killing are decreased. The effects of normal platelets containing serotonin and of reagent serotonin on the subnormal microbicidal activity of CH leukocytes were evaluated. The peripheral blood leukocytes of the beige mouse, an animal model with CH syndrome, were used with Staphylococcus aureus as the bacterial challenge. Addition of as few as two normal platelets/leukocyte resulted in normal levels of microbicidal activity of CH leukocytes. A similar normalization of leukocyte function was seen when 1-100-micrometer serotonin was added to the incubation mixture. Based on this work and work of others, a plausible explanation for these observations is that normal platelets interact with CH leukocytes, releasing serotonin, which results in reversal of the CH leukocyte defect in bacterial killing.