Although an increase in urine flow rate has been shown to augment urinary prostaglandin E (PGE) excretion, the relationship between these two variables has not been quantitated. Because we have previously shown that water immersion to the neck induces diuresis and augmentation of PGE excretion, we utilized water immersion to the neck to assess kinetically the relationship between changes in flow rate and PGE excretion. Fourteen normal male subjects were studied twice during 4 hours of water immersion to the neck, once after 11 hours of fluid deprivation and again during moderate hydration. PGE excretion as determined by radioreceptor assay was measured each hour. When subjects deprived of fluids underwent immersion to the neck, flow rate increased from 0.5 ml/min (control) to 1.5 ml/min, and PGE excretion rose from 1.4 to 2.6 ng/min (both p less than 0.01). In contrast, when subjects were studied during hydration, flow rate increased from 4.1 to 7.2 ml/min and PGE excretion increased from 8.1 to 13.0 ng/min at the same time intervals (both p less than 0.01). There was a significant positive correlation between flow rate and PGE excretion during both fluid deprivation and hydration. Were there an effect, independent of flow rate, of hydration on PGE, the slope of these two regression lines would differ. When the regression line slopes of these relationships were analyzed by the F test, there was a statistically significant (p less than 0.01) difference between the two regression coefficients. Our data suggest that, in addition to the previously characterized relationship between flow rate and PGE excretion, there is also a direct effect of hydration on PGE excretion.