The relationships between urinary prostaglandin E excretion and urine flow rate were evaluated in 11 conscious mongrel dogs during antidiuresis, maximal water loading, vasopressin administration during maximal water loading, and mannitol infusion. Urine flow rates between 0.21 and 15.1 ml/min were achieved. Urinary prostaglandin E excretion rates, determined by a membrane receptor assay, varied directly with urine flow rates (r = 0.908). Vasopressin administration (34--540 microU . kg-1 . min-1) resulted in a fall, rather than the expected rise, in urinary prostaglandin E excretion. When the concentration of prostaglandin E in the urine was plotted against urine flow rate, the demonstrated relationship appeared most consistent with passive diffusion. Mannitol infusion increased urine flow rates to levels comparable to the levels seen with maximal water loading but did not result in a fall in plasma osmolality. Urinary prostaglandin E excretion rates, however, were not distinguishable from those in the previous group. These data demonstrate that urinary prostaglandin E excretion rates are determined, to a great extent, by urine flow rate and that the significance of the interpretation of elevated excretion levels of these lipids in diuretic states may have to be reevaluated.