Circadian fluctuation in tumor blood flow of the rat subcutaneous tumor was investigated. Tumor tissue blood flows in the daytime zone (10 a.m. to 4 p.m.) and in the nighttime zone (10 p.m. to 4 a.m.) in both the first phase (doubling time of tumor volume = 1.7 days) and the second phase (doubling time of tumor volume = 5.7 days) of growth of the LY80 tumor in rats were measured using the hydrogen gas clearance technique. In the first phase of tumor growth, the tumor blood flow was 20.3 +/- 12.2 ml/min/100 g in the daytime zone (n = 22) and 46.6 +/- 19.3 ml/min/100 g in the nighttime zone (n = 22). In the second phase, tumor blood flow was 9.6 +/- 5.7 ml/min/100 g in the daytime zone (n = 45) and 19.4 +/- 8.2 ml/min/100 g in the nighttime zone (n = 38). Tumor blood flow in the nighttime zone was significantly higher than that in the daytime zone (first phase, P less than 0.001; second phase, P less than 0.001). However, there were no significant differences in the mean arterial blood pressure, tumor size, and body weight of rats between the daytime zone and the nighttime zone. There was also a marked difference in the effect of angiotensin II-induced hypertension on tumor blood flow between the daytime zone and the nighttime zone. These results suggest that circadian fluctuations in tumor blood flow should be carefully considered when developing strategies to maximize the effectiveness of cancer therapy in relation to the flow rate of circulating blood.