Ureteral obstruction leading to pain seems to be related to an increase of renal prostaglandins (PG). We designed a prospective double-blind, placebo controlled protocol for evaluating the effect of indomethacin, a PG-synthetase inhibitor, in the prophylaxis of ureteral colic following extracorporeal shock wave lithotripsy (ESWL). Sixty patients undergoing ESWL were randomized into two groups, group 1 (study group) received 50 mg indomethacin capsule three times daily and group 2 (control group) received multiple-vitamin tablet three times daily. Twenty-four hours urine samples were collected before and three days after ESWL was performed for PGE2 (predominant renal PG) determination. Subjective pain after ESWL was recorded with pain score (0-10 degrees). Oral codein or pethidine injection were available for relieving pain following ESWL. The pain score, analgesic requirement and urinary PGE2 in pre- and post-ESWL were used to compare the two groups. The pain score was 4.00 +/- 0.25 and 3.00 +/- 0.25 in the control and study groups respectively; it had a statistically significant difference (p < 0.01). In control group, 12 and 14 patients required 23 doses of codein and 18 doses of pethidine. In the study group, three and four patients required five doses of codein and eight doses of pethidine. The difference was statistically significant (p < 0.05). In the control group, the mean pre- and post-ESWL urinary PGE2 was 305 +/- 65.8 and 474 +/- 101 micrograms/24-hr respectively. In the study group, the mean pre- and post-ESWL urinary PGE2 was 289 +/- 60.7 and 186 +/- 26.5 micrograms/24-hr respectively.(ABSTRACT TRUNCATED AT 250 WORDS)