The effect of zymosan-activated serum samples, obtained from patients with acne who were receiving oral tetracycline hydrochloride therapy, on the chemotaxis and random migration of autologous polymorphonuclear leukocytes (PMNLs) and PMNLs from control donors was assayed in a Sykes-Moore chamber by a double-filter technique. Cells incubated with autologous serum specimens from these patients demonstrated significant suppression of both random migration and chemotaxis, with the greatest effect seen at a dosage of 1 g daily and a significant effect found at all dosage levels. When zymosan-activated serum samples from these patients were assayed with control donor PMNLs, similar inhibitory effects were shown. Assays of control sera and PMNLs from tetracycline-treated patients with acne showed the least degree of inhibition of chemotaxis. Although the mechanism of action is unclear, tetracycline appears to have a direct effect on neutrophil movement.