Quantitation of the 99mTc-diethylenetriaminepentaacetic Acid (DTPA) scan yields by uptake analysis an estimate of individual kidney glomerular filtration rate (IKGFR) and by deconvolutional analysis an estimate of the mean transit time (MTT) of the non-reabsorbable tracer through the kidney. The whole kidney MTT is compounded of the renal parenchymal MTT and the rate of pelvic clearance; both functions are influenced by prevailing rates of salt and water excretion. The present study was undertaken to investigate the effect of physiological variations on the normal DTPA scan. The contralateral normal kidney in 11 children with suspected unilateral urinary tract obstruction were studied twice, first with an early morning scan (EMS) and second, 24 h later, following hypotonic volume expansion (HVE). A strong correlation was shown between urine osmolality and MTT. IKGFR was independent of the state of hydration, but in comparison to mild hydration, HVE shortened significantly (P less than 0.001) the normal whole kidney MTT, with less effect on parenchymal MTT (P less than 0.01) and therefore has its predominant effect on pelvic clearance. We advise caution in the interpretation of whole kidney transit time analysis without standardization of salt and water excretion rates. Parenchymal transit time offers a potentially useful clinical index.