Stimulation of human lymphocytes with Con A resulted in the liberation of a soluble lymphokine that increased the permeability of guinea pig skin capillaries. This factor, termed vascular permeability factor (VPF), was characterized by physicochemical methods. Upon gel filtration chromatography on Sephadex G-100, it eluted in a narrow peak with an apparent molecular weight of 12,000 daltons. The sedimentation rate of VPF, estimated by sucrose density gradient ultracentrifugation, was 1.8 S. Polyacrylamide gel electrophoresis showed the biologic activity to migrate in the beta region; the factor displayed a pI of 6.4 upon isoelectric focusing. These characteristics allow VPF to be distinguished from other human lymphokines.