Tracer microinjection studies were used to grossly locate the nephron site of altered calcium transport following D-glucose loading. Superficial proximal and distal nephrons were injected with a solution containing 45Ca and either D-glucose or L-glucose (as control). Tubule calcium transport was assessed from the recovery of radioactivity in the final urine. 45Ca recoveries from early proximal microinjections were comparable in the two groups (2.63 +/- 0.68 vs. 3.70 +/- 1.19%). However, 45Ca recoveries from late proximal microinjections were significantly higher than D-glucose was included in the injectate (7.39 +/- 1.34 vs. 2.83 +/- 0.67%, P < 0.05). 45Ca recoveries from distal microinjections were also significantly higher in the D-glucose group (87.6 +/- 2.43 vs. 71.0 +/- 2.92%, P < 0.001). These data suggest that the effects of D-glucose on renal calcium handling are mediated at the level of the distal tubule, thick ascending limb of the loop of Henle and/or pars recta. The precise mechanisms involved are not known.