An evaluation of the literature indicated that certain aspects of the disposition kinetics of iothalamate, important to the accurate determination of glomerular filtration rate in dogs and humans, remain to be resolved. The simultaneous clearances of iothalamate and inulin in 5 dogs were determined at three steady-state iothalamate plasma levels (2, 10, and 40pg m1-I) following various rates of intravenous infusion. The iothalamate clearances, both renal and non-renal, were concentration-independent. The overall mean non-renal clearance was 18 per cent (ranging from 9 to 25 per cent) of its plasma clearance. The mean iothalamatehnulin renal clearance ratio was about 0.84 with individual values ranging from 0.72 to 0.95. The significant (4-26 per cent) plasma protein binding of iothalamate in these dogs was the main reason for the lower-than-unity clearance ratios obtained. The literature indicates the existence of up to 25 per cent of non-renal elimination in humans with normal renal function; this is comparable to the present results obtained with dogs but contrary to the assumption, sometimes reported in the literature that non-renal elimination is essentially absent in humans. Binding of iothalamate to plasma proteins from humans was not found in the present study. The above results suggest that for accurate glomerular filtration rate determination in humans and dogs, especially for those with renal impairment. renal clearance rather than plasma clearance should be used, and in the case of dogs it should also be corrected for plasma protein binding. Iothalamate in plasma and urine was analysed by a simple, micro high-performance liquid chromatographic method with UV detection.