To evaluate the risk of significant plateletpheresis-induced thrombocytopenia in normal volunteer donors undergoing plateletpheresis less frequently than every 56 days and to help understand factors influencing platelet yield in these donors, pre- and postapheresis platelet counts (X 10(3)/microliter) and platelet yields were analyzed from 916 plateletpheresis procedures (Fenwal CS-3000) on 607 donors (405 men, 202 women). The mean preapheresis platelet count was 265 +/- 59 (SD) (range 155-650) (men 256 +/- 55 [170-444]; women 284 +/- 65 [155-650]; P less than .001, t-test). After an average platelet yield of 4.08 X 10(11), the mean postplatelet count was 185 +/- 46 (range 72-420) (men 184 +/- 42 [80-345]; women 194 +/- 52 [72-500]; P less than 0.1). The percent decrease in platelet count (mean 29.4 +/- 13, range -28.1-65.5) had positive correlations with platelet yield (P less than .01, r = 0.10), predonation platelet count (P less than .001, r = 0.29), and age (P less than .01, r = .10) and a negative correlation with weight (P less than .001, r = 0.18) Both the percent decrease and platelet yield were significantly higher in women than in men (P less than .001, t-test), and platelet yield was best predicted by preapheresis platelet count in both sexes (r = 0.65). The effects of plateletpheresis on donor platelet count thus vary widely among donors. Although a decrease of greater than 50% was not a rare event (5.9% of all procedures), in only three instances (0.3%) was the actual postapheresis platelet count below 100 (72, 94, 95). Thus, plateletpheresis in normal donors appears unlikely to produce clinically significant thrombocytopenia immediately after apheresis.