The kidney possesses the enzymatic steps required for the biosynthesis of histamine and this autocoid may play a role in modulating renal hemodynamics and the local inflammatory response to immunologic injury. We, therefore, measured urinary histamine. N-methylhistamine and N-methylimidazole acetic acid concentrations in patients with proteinuria due to a variety of disease states – idiopathic nephrotic syndrome (n = 19), systemic lupus erythematosus (n = 10), refractory focal segmental glomerulosclerosis (n = 10) and control patients (n = 16). Urinary histamine concentration was significantly reduced in treatment-responsive idiopathic nephrotic syndrome during disease relapse compared to remission (16.6 ± 3.6 vs. 28.4 ± 4.8 μmol/mol creatinine, p < 0.02). The levels were also depressed in children with other causes of persistent proteinuria, including systemic lupus erythematosus (10.3 ± 4.0 μmol/mol creatinine) and focal segmental glomerulosclerosis (14.6 ± 2.8 μmol/mol creatinine) compared to normal controls (31.4 ± 4.7μmol/mol creatinine). The decreased urinary excretion of histamine and its metabolites in patients with proteinuria may be a result of immunologically mediated mesangial cell injury or represent a compensatory hemodynamic response to limit urinary protein losses.