Twelve non-diabetic volunteers (age = 39 +/- 13 years, BMI = 23.5 +/- 3.5) undertook a randomized double-blind placebo-controlled crossover study in which they ingested either 120 mg of EGb 761 or a placebo daily for 3 months and then switched to the other test capsules for the next 3 months. Platelet aggregation in platelet-rich plasma (PRP) was performed at the end of each 3-month arm, with or without 1-min incubation with graded doses of EGb 761. In the placebo cycles, AA-stimulated TXB2 production was 2581 +/-1337 pg/10(6) platelets (range 897-5485) compared to 1668 +/- 992 pg/10(6) platelets (range 6-1668) in the EGb 761 cycles (p < 0.005). Incubation of PRP with EGb 761 (150 microg/ml) completely inhibited platelet aggregation accompanied by inhibition of TXB2 synthesis in all subjects both in the placebo (<200 pg TXB2/10(6) platelets) and EGb 761 cycles (< 120 TXB2/10(6) platelets) (p < 0.0001). These results support EGb 761-mediated inhibition of platelet TXB2 synthesis in vivo.