Increased platelet aggregability has been shown in hypercholesterolemia, and stirring-induced spontaneous aggregation in whole blood is increased in insulin-dependent diabetes mellitus (DM). We have determined spontaneous aggregation in citrated (10 mM) whole blood, from 27 primary dyslipidemic patients (DYS; 14F, 13M), 16 male non-insulin-dependent DM (NIDDM) patients, and 17 normolipidemic controls (N; 6F, 11M), using platelet counting to quantify aggregation. Spontaneous aggregation was significantly higher, both in the female DYS group (median 30% [interquartile range 25,50], P < 0.005) and the NIDDM group (33% [25,41], P < 0.005), than in the N group (17% [12,27]), but did not differ significantly in the male DYS group (23% [10,33]). Similar results were obtained in the presence of indomethacin (25 mumol/l) to prevent artefactual thromboxane (TX) A2 formation, indicating that increased spontaneous aggregation was TXA2-independent. Interestingly, increased spontaneous aggregation appeared to be independent of serum cholesterol and triglyceride concentrations, as well as age and sex per se. We conclude that spontaneous platelet aggregation was increased both in female primary dyslipidemic patients and NIDDM patients, but not in male DYS patients. The clinical significance of increased spontaneous platelet aggregability is that it may favour shear-induced aggregation which may occur at critical arterial stenoses in vivo leading to thrombus formation.