Polymorphonuclear granulocytes (PMNs) and lymphocytes from healthy persons were incubated in varying concentrations of erythromycin and RU 28965, a new macrolide antibiotic. Incubation in erythromycin - even in high dilutions - caused a significant increase in the percentage of PMNs bearing receptors for the Fc portion of IgG (Fc gamma R) and for C3b (C3bR) as measured by rosette formation with EA (erythrocyte-antibody) and EAC (erythrocyte-antibody-complement) indicator cells. This effect could not be removed by extended washing of the cells. Incubation in RU 28965 had a similar effect, except for a decrease in EA and EAC rosetting cells at high concentrations (200 mg/l). Phagocytosis, as measured by chemiluminescence, and random migration of PMNs were unaffected by erythromycin. Chemotaxis under agarose was decreased after incubation in erythromycin or RU 28965. Erythromycin incubation increased the percentage of lymphocytes bearing receptors for sheep erythrocytes (E), but had no effect on the proportion of lymphocytes rosetting with EA or EAC, or on lymphocyte responses to mitogens PHA, conA, or PWM.