The isolated perfused rat kidney was used to study the effects of parathyroid hormone-related protein (PTHrP) on renal cyclic AMP (cAMP) and electrolyte excretion. A perfusate of PTHrP(1-34) increased cAMP excretion from 0.14 ± 0.09 (S.E.M.) nmol/l glomerular filtrate (GF) in controls to 24.67 ± 5.14 (P < 0.01) and decreased calcium excretion from 0.278 ± 0.033 to 0.162 ± 0.011 μmol/l GF (P < 0.01). Human PTH(1-34) (0.7 nmol/l) caused no significant change in calcium excretion, whilst the rise in cAMP excretion was similar to that with PTHrP. PTHrP(1-34) (7 nmol/l) further increased cAMP production to 366.7 ± 100.8 nmol/l GF (P < 0.01), higher than the rise with hPTH(1-34) (7 nmol/l) which was 76.7 ± 46.8 (P < 0.05). With the higher concentrations of both peptides (7 nmol/l), calcium excretion was further reduced to 0.090 ± 0.009 μmol/l GF (P < 0.01), whilst phosphate excretion increased with both PTHrP and PTH. PTHrP (7 nmol/l) caused a fall in urinary pH compared with controls (P < 0.05). At low and high concentrations of both hormones urinary pH was lower with PTHrP than hPTH (P < 0.01). Thus PTHrP, like PTH, acts on the kidney to increase cAMP and phosphate excretion and reduce calcium excretion, but PTHrP may be more effective. Disparate effects on urinary pH could be reflected in the clinical features of humoral hypercalcaemia of malignancy.