To obtain the maximum prophylactic effect of intravesical chemotherapy on the bladder tumor recurrence treatment should be started early. Since 1983, we have been initiating prophylactic instillation of doxorubicin hydrochloride (DXR) on the first post-transurethral resection (TUR) day. This study was conducted to define serum uptake of DXR and systemic toxicity in the early post-TUR period. Fifteen TURs were carried out on 14 patients with superficial bladder carcinoma. DXR (30 mg) in normal saline (30 ml) was intravesically administered 1, 3, 5, 7 and 14 days after TUR, and every 4 weeks thereafter. DXR solution was kept in the bladder for 2 hours. The serum DXR concentration was measured 30 minutes and 2 hours after the instillation through 1 to 5 days after TUR. Intolerable vesical irritability was seen in 4 of 60 instillations. No systemic side effects, however, were observed. Three of 24 samples contained a detectable level (10 ng/ml) of DXR on the post-TUR day 1, 6 of 22 samples on the post-TUR day 3, and 6 of 14 samples on the post-TUR day 5. Overall, 15 of 60 samples contained more than 10 ng/ml DXR. The highest serum DXR level was 47 ng/ml at the post-TUR day 1. Frequency of detection and average levels of serum DXR in 30-minute and 2-hour samples were not significantly different. Average concentrations in patients with multiple or diffuse tumor and solitary tumor were also not significantly different. These results indicate that intravesical instillation starting within 24 hours after TUR does not produce significant serum uptake of DXR, and systemic toxicity can thereby be avoided.