Nine volunteers received a 500 mg oral dose of tetracycline hydrochloride in three trials: A: With 180 ml water; B: With 30 gm colestipol in 180 ml water; C: With 30 gm colestipol in 180 ml orange juice. Tetracycline concentrations in multiple urine samples collected during 48 hours after each dose were determined by high pressure liquid chromatography. The three trials did not differ significantly in 48 hour cumulative urine volume (3086 vs 3207 vs 3194 ml for Trials A, B, and C). However, the three trials differed significantly in 48 hour excretion of tetracycline (F = 28.2; P less than .001). During Trial A, mean excretion was 237 mg; this was significantly (P less than .05) reduced to 109 mg in Trial B and 104 mg in Trial C. However, Trials B and C were not different. Thus, coadministration of tetracycline with colestipol significantly impairs tetracycline absorption by more than 50%. Mixing colestipol with orange juice does not alter colestipol-induced impairment of tetracycline absorption.