The pathogenesis of minimal-change nephrotic syndrome (MCNS) is obscure. It has been postulated that this glomerular disease may be a systemic disorder of cell-mediated immunity. IL-12 is a heterodimeric cytokine that is produced primarily by antigen-presenting cells and plays a primary role in the induction of cell-mediated immunity. To gain insight into the involvement of this cytokine, in vitro IL-12 levels were assessed in patients with MCNS and IgA nephropathy (IgAN) who were in either a stable or active clinical condition. The levels were compared with values in healthy controls. Significantly increased spontaneous and lipopolysaccharide (LPS)-stimulated release of IL-12 was detected in peripheral blood monocyte (PBM) cultures of MCNS and IgAN patients with the nephrotic syndrome (NS) compared with those of normal controls. Moreover, when individual MCNS patients were followed through their clinical illness, IL-12 levels were increased during the active phase and normalized as the patients went into remission. The amounts of IL-12 are significantly correlated with the levels of vascular permeability factor (VPF) in MCNS patients. This study describes a correlation between in vitro IL-12 release by PBM from two types of nephrotic patients and their disease activity, as well as a correlation with release of VPF by the same cultures. The study contributes to the understanding of this class of diseases and the observations may have a prognostic/diagnostic value.