Production of 12-L-hydroxy-5, 8, 10-heptadecatrienoic acid (12-HHT) from platelets and bleeding times were studied in 32 males during acetylsalicylic acid (ASA) treatment and 1 and 2 weeks after withdrawal. All patients (age 42-77 years) had ASA treatment because of angina pectoris. The metabolite 12-HHT is formed in the same amount as the proaggregatory and vasoactive metabolite thromboxane A2. Initially the daily ASA dose was 75 mg (n = 15), 160 mg (n = 12) or 250-300 mg (n = 5). In all patients, median 12-HHT level increased from 40 to 240g/750 x 10(6) platelets (P < 0.001) 1 week after withdrawal of ASA, and four patients had abnormally high values. Median bleeding time decreased from 312 to 268 s (P = 0.003) in the 75 mg group and from 315 to 235 s in the 160 mg group (P = 0.01). Two weeks after withdrawal of ASA, median 12-HHT was 390g/750 x 10(6) platelets and eight patients (25%) had abnormally high values. One patient still had a prolonged bleeding time. Wide interindividual variations were observed in all groups. Our results indicate that rapid withdrawal of ASA, may cause abnormally high 12-HHT levels reflecting increase of thromboxane A2 with possible hazardous effects in patients with cardiovascular disease.