Cytosolic calcium concentration ([Ca2+]i) in platelets during resting state and when stimulated by thrombin were measured in 7 alcoholic dependent patients in the state of withdrawal (AW) who were receiving diazepam, 7 bipolar manic patients (BM) who were receiving haloperidol, 15 drug free chronic schizophrenic patients (CS) and 26 normal controls (NC). Resting [Ca2+]i in these groups were quite similar at (mean +/- SEM) 112 +/- 20 nM, 127 +/- 18 nM, 103 +/- 16 nM and 106 +/- 8 nM respectively. Increase in platelet [Ca2+]i in response to 0.1 U/ml thrombin was expressed as delta[Ca2+]i and its percentage over resting [Ca2+]i as %[Ca2+]i. Both delta[Ca2+]i and %[Ca2+]i were significantly higher (p = 0.006 and 0.0045 respectively, ANOVA, Waller-Duncan) in AW (433 +/- 71 nM, 417 +/- 58%) than the other groups: NC (223 +/- 25 nM, 225 +/- 23%), BM (309 +/- 38 nM, 260 +/- 31%), and CS (261 +/- 34 nM, 280 +/- 29%) respectively. In vitro incubation of platelets from NC with diazepam or haloperidol did not affect the resting [Ca2+]i and %[Ca2+]i. The enhanced [Ca2+]i response to thrombin in platelets of AW is unlikely to be due to diazepam. It may indicate an abnormality in platelets during the withdrawal phase. Treatment with haloperidol resulted in slightly higher [Ca2+]i in platelets of BM. Platelet [Ca2+]i in drug-free CS was not different from NC.