The role of the spleen as a reservoir capable of adding platelets to the circulating blood cells has been well documented in animals but poorly documented in humans. As part of a program of platelet cryopreservation, we have intensively plateletpheresed a group of patients with acute leukemia in remission who had undergone splenectomy. The results of the 64 plateletphereses in these 11 patients (average platelet yield 4.2 X 10(11) +/- 2.4, range 1.2-12.4) were compared with 50 consecutive plateletphereses in nonsplenectomized leukemia patients (average yield 4.9 X 10(11) +/- 3.2, range 2.1-18.3) and 50 consecutive plateletphereses in normal donors (average yield 3.8 X 10(11) +/- 1.4, range 1.7-7.6). There was no difference in the prepheresis platelet counts among the three groups. Plateletphereses were done in 1.5-3 hr by intermittent flow differential cell centrifugation technique. The expected platelet yield was calculated by multiplying the pre-platelet count - (pre-hct/post-hct X post plt count) by the estimated blood volume (70 ml/per kg body weight). The mean ratios of the observed platelet yield to expected platelet yield were similar for the nonsplenectomized leukemia patients (mean ratio = 1.32 +/- 0.50, range 0.73-3.04) and normal donors (mean ratio = 1.31 +/- 0.49, range .52-2.9), implying mobilization of platelets from outside of the blood pool. In contrast, in the splenectomy group, the mean ratio (0.76 +/- 0.32, range 0.31-2.9) was significantly lower (p less than .001). These data indicate that there is replenishment of the circulating platelet pool by the spleen in response to the rapid removal of platelets.