Currently, the frequency of granulocyte donation is limited by the prolonged circulation of hydroxyethyl starch (HES). We conducted a Phase I, uncontrolled, multicenter trial to evaluate both the efficacy and safety of a rapidly excreted low-molecular-weight analog of HES (LMW-HES). Seventy-five donors underwent 179 centrifugation leukapheresis procedures using LMW-HES as the red-cell-sedimenting agent. The efficacy of LMW-HES was established by harvesting adequate numbers of leukocytes. Most granulocyte concentrates contained at least 20 X 10(9) neutrophils when 8 l of blood was processed from donors optimally stimulated with steroids. The safety of LMW-HES was documented by the detection of almost no clinically significant adverse effects. In only 1.7 percent of procedures did donors require special attention, and only 1 of 179 procedures (0.6%) was permanently discontinued. Results of laboratory studies were usually normal or their values decreased transiently (approximately 15-25%) as a consequence of plasma volume expansion (dilution). Based on previous experience with HES, LMW-HES and HES perform comparably during leukapheresis. When commercially available, use of this new, rapidly excreted analog should permit more frequent leukapheresis donation.