The urinary excretion of prostaglandin E2 (PGE2) was measured in conscious rats under conditions which produced either acid or alkaline urine, but a similar change in fluid and solute excretion. Oral isotonic saline increased both urine flow and sodium excretion but did not alter urinary PGE2 output (which remained constant at 80 pmol/3 h per rat) or urine pH (6.2). When the urine was made alkaline (pH 7.8) by oral sodium bicarbonate or carbonate, urinary PGE2 was approximately 3-fold greater (P less than 0.001) than the control (pH 6.2). The urine flow and sodium output were also increased. When the urine was made acidic (pH 5.7) by oral ammonium chloride, urinary PGE2 excretion was reduced (P less than 0.01) to approximately half the control output. The urine flow and sodium output increased. Within a group of 12 rats receiving oral isotonic saline a positive linear correlation coefficient (P less than 0.002) was established between urine pH and PGE2 excretion. The results indicate that urine pH may be a determinant of PGE2 excretion in unrestrained, conscious rats. It seems likely that this effect of pH is mediated by a change in the passive reabsorption of PGE2 in the distal nephron, although alternative explanations such as altered tubular secretion or synthesis cannot be categorically excluded.