We systematically compared the individual effects of infusion rate, solution osmolality, and temperature on plasma solute secretion during luminal perfusion of an isolated 90-cm jejunal segment in the conscious and otherwise normal dog. The control state was perfusion at a rate of 3 ml/min of a 25 degrees C temperature solution containing (mM): NaCl, 40; NaHCO3, 10; and mannitol, 220 (320 mosm/kg). Increasing infusion rate from 3 to 9 ml/min increased secretion of Na-, K+, and urea (P < 0.05); further elevation of infusion rate to 18 ml/min increased only Cl- and urea secretion (P < 0.05). Thus, increasing infusion rate of the control solution had only a limited role in promoting solute secretion. In contrast, perfusion solutions elevated in osmolality to 600 and 1200 mosm/kg by mannitol progressively augmented the secretions of water, Na-, K+, Cl-, HCO3(-), Ca2+, and urea (P < 0.05). Perfusion of the 1200 mosm/kg solution produced solute secretions either equivalent to or greater than secretions obtained during 18-ml/min perfusion with the control solution, despite the fact that 1200 mosm/kg perfusion yielded about one-third the effluent volume. Warming of the control solution to progressively increase infusion temperatures from 29 to 41.9 degrees C increased (P < 0.05) water, Na+, K+, and Cl- secretion and HCO3 absorption linearly. Urea secretion increased (P < 0.05) above a temperature threshold of 38-38.9 degrees C. In conclusion, perfusion solution infusion rate, osmolality, and temperature are unique independent determinants of plasma solute secretion by jejunum. These data are the basis for optimizing the physical determinants of jejunal clearance for applying jejunal perfusion to treatment of renal failure.