The pattern of disease recurrence was examined in 75 patients with clinically undetectable positive urinary cytology results following a complete response to intravesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder cancer. A complete response was defined as negative cystoscopy and biopsy findings, urine cytology and flow cytometry (when available) for at least 1 year following therapy. Urinary cytology was positive in the absence of clinical disease at a median of 25 months (range 12 to 96) after BCG administration. Clinically recognizable disease (defined by a positive biopsy or visible papillary tumor) developed at a median of 6 months (range 2 to 60) after positive cytology was detected in 62 patients (83%), while 13 (17%) had persistently positive cytology results without an obvious source at a median of 6 months (range 2 to 29). The bladder was the single most common site of recurrence, with 39 recurrences developing in 36 patients (58%, 3 of whom had recurrent cancer after a complete response to each of 2 separate courses of BCG): 30 (77%) were superficial (stages Ta in 2, Tis in 25, Tis/T1 in 2 and T1 in 1) and 9 (23%) were invasive (stage T2+). Median interval to the detection of bladder recurrence following a positive cytology result was 6 months (range 2 to 50). Upper urinary tract disease developed at a median of 7 months (range 2 to 41) in 11 patients (18%), while 7 (11%) had a prostatic recurrence at a median of 5 months (range 2 to 60). There were 9 synchronous bladder and prostate (5) or upper tract (4) recurrences in 8 patients (13%) at a median of 22 months (range 2 to 40) in the former group and 15.5 months (range 3 to 20) in the latter group. Overall, of 75 sites of recurrence in 62 patients 48 (64%) were in the bladder, 15 (20%) in the upper urinary tract and 12 (16%) in the prostate. High risk patients with superficial bladder cancer who have clinically unconfirmed positive urinary cytology results following a complete response to intravesical BCG therapy require aggressive evaluation of intravesical and extravesical sites to detect the presence of persistent or progressive in situ or invasive disease.