The effects of thalidomide on chemotaxis of normal human peripheral blood PMN leukocytes have been studied in vitro. The chemotaxis factor was generated by interacting normal human serum with bovine gamma globulin-antibovine-gamma globulin immune complexes. At concentrations of 1, 10, and 100 microgram/ml, thalidomide failed to inhibit the chemotactic factor. At the same concentrations, erythromycin caused a marked inhibition of chemotaxis. Pre-incubation of PMNs with thalidomide or erythromycin caused a marked, dose-independent inhibition of chemotaxis. Random mobility did not appear to be affected. Inhibition of PMN chemotactic ability by thalidomide may account for its ability to improve inflammatory dermatoses, such as aphthosis.