This study on the increase in albumin in the urine of patients with superficial bladder cancer after intravesical bacillus Calmette-Guérin (BCG) treatment was initiated on the basis of two facts. First, extravasation of serum albumin could be expected as a result of the BCG-induced delayed-type hypersensitivity reaction in the bladder wall. Second, appearance of albumin in the urine was a possibility as cytokines also appear in the urine, although probably after being produced suburothelially by infiltrating leukocytes. Albumin and the cytokines interleukin (IL)1 beta, IL2, IL6, and tumor necrosis factor alpha (TNF alpha) were determined in urine from 20 patients treated with 6 weekly intravesical BCG instillations, collected prior to each instillation and 2, 4, 6, 8, 12, and 24 h thereafter. The mean concentration of albumin in pre-therapy specimens was 112 +/- 118 (range 2-432) micrograms albumin/ml urine, approximating 14 +/- 14 micrograms/mumol creatinine (creat) (n = 15), which was comparable to the mean pre-instillation value of 16 +/- 32 micrograms/mumol creat (n = 96). A significant increase in urinary albumin during the 6 weeks of BCG treatment was observed (P < 0.001). However, a large variation existed between individual patients and in some patients no reaction was seen. Maximum albumin concentrations were observed after instillations 3-6. A significant correlation between albumin and concentration of the cytokines IL1 beta, IL2, IL6, and TNF alpha was found (P < 0.01), correlation coefficients (r) being 0.56, 0.56, 0.67, and 0.71 (n = 418), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)