To pursue the concept that “activated” platelets (plats) in vivo might be deficient in 5HT (as well as being deficient in PF4 - Abstract submitted), we collected citrated blood from 39 “healthy” controls aged 15–50 yrs and from 14 patients (25–75 yrs), 2–8 days after major surgery. The plat 5HT, the 5HT uptake and plasma 5-hydroxyindoles (PPP 5HTs) were measured fluorometrically and the mean plat, volume (MFV) was measured using a Coulter S plus counter.In health (n = 39) with increasing age the MPV (correlation: r = 0.45, p<0.01), the plat 5HT (r = 0.62, p<0.001) and 5HT uptake (r = 0.45, p<0.0l) all decreased while the PPP 5HIs increased (r = 0.71, p<,0.00l). The plat 5HT was also positively correlated with 5HT uptake (r = 0.42, p<0.01) and with MPV (r = 0.45, p<0.01) and negatively with PPP 5HIs (r = 0.43, p<0.01).After operations (n = 14) irrespective of age the plat 5HT was lower than the controls' (p<.0.001) and the MPV and 5HT uptake were low, but not significantly so. The plat, count was significantly lower than the controls (p<0.001). Again the plat 5HT correlated with MPV and 5ê uptake.Differential centrifugation of normal PRP into platelet sub-populations with differing MPVs confirmed the correlation between MPV and plat 5HT.It is concluded that both operations and increasing age are associated with the appearance of small relatively empty plats “exhausted” of 5HT which cannot take up 5HT. Have these plats been partially activated and undergone release with a subsequent decrease in volume? Alternatively, are large platelets relatively full of 5HT removed from the circulation, or not produced? (These findings support and extend the findings of Shuttleworth et al, Blood March 1981: in press).