Visceral leishmaniasis (VL) remains a major health problem in Kenya and other parts of Africa, Central America and Asia. Currently, splenic aspirate smear and culture are the standard methods of monitoring therapy and relapse. Acute phase reactant markers, C-reactive protein (CRP), serum amyloid A protein (SAA) and alpha 1-acid glycoprotein (AGP) were evaluated as less invasive techniques for monitoring therapy in 59 patients with VL before, during and after therapy. CRP, SAA and AGP were elevated in VL patients at admission and the concentrations decreased with effective therapy to reach normal levels by the end of therapy (SAA and AGP) or by 3 months follow-up (CRP). Two groups of patients were selected on the basis of rate of parasite clearance. The acute phase protein concentrations were significantly raised in those slower to clear parasites. Analysis of sensitivity and specificity of acute phase proteins as predictors of parasite clearance suggested that they might represent useful non-invasive markers for monitoring disease activity, response to therapy and relapse in VL.