The pharmacokinetics of diltiazem and its major metabolites, deacetyldiltiazem and N-monodemethyl-diltiazem, were studied after single and chronic oral administration in eight patients aged 45 to 69 years with unstable angina pectoris, treated by diltiazem, 120 mg t.i.d. After a single oral dose the time to peak plasma diltiazem concentration was 3.4 (2.1 to 5.0) hours and the elimination half-life was 6.6 hours (4.4 to 10.8 hours). These were unchanged after repeated oral administration (16 to 19 doses). The mean trough (8 hours after administration) plasma diltiazem level after six consecutive doses was 167 micrograms/L (63 to 286 micrograms/L) and was thereafter stable. With chronic administration the AUC increased by a factor of 2.24 +/- 0.31 (SEM; P less than 0.01). Plasma protein binding of diltiazem in these patients ranged from 83% to 93% whereas deacetyldiltiazem binding ranged from 58% to 75%. Plasma protein binding was independent of drug concentration and duration of treatment. Thus an average dose of 120 mg diltiazem given every 8 hours would appear to be a suitable regimen of treatment in most patients with angina pectoris, although users should be aware that there is a significant interpatient variability in steady-state diltiazem concentrations and that a significant accumulation of diltiazem occurs with chronic therapy.