Counterimmunoelectrophoresis was used to detect Cryptococcus neoformans capsular polysaccharide in the body fluids of infected patients. Using rabbit anti-C. neoformans A15 globulin, counterimmunoelectrophoresis detected 1.25 microgram of purified cryptococcal polysaccharide per ml of cerebrospinal fluid (CSF) or urine and 2.5 microgram per ml of serum. When the body fluids were subjected to a hundredfold concentration prior to testing, as little as 25 ng of purified cryptococcal polysaccharide/ml CSF or urine and 80 ng/ml serum was detected. Among patients with cryptococcal meningitis, counterimmunoelectrophoresis detected polysaccharide in the CSF when the India-ink examination was negative. Using counterimmunoelectrophoresis, the concentrations of polysaccharide antigen in the body fluids of these patients could be estimated. Specificity of the rabbit anti-C. neoformans A15 globulin was evaluated. There was no crossreaction that detracted from its diagnostic usefulness. Rheumatoid factor was not a source of false-positive tests. Counterimmunoelectrophoresis is a useful technic for establishing a rapid, specific serologic diagnosis of cryptococcosis.