Classic experimental immunologic orchitis was induced in guinea pigs by injection of homologous testis homogenate in complete Freund's adjuvant. Blood samples were obtained periodically for 45 days and the animals were hemicastrated on the 8th day after sensitization. By the 8th day, cytophilic activity was found in the serum simultaneously with several foci or orchitis. Significant levels of this activity were found until day 29, but it was absent in animals sensitized with an unrelated antigen or with complete adjuvant alone. Low and transitory levels were detected in some guinea pigs when antigen was administered with incomplete Freund's adjuvant. It is concluded that cytophilic activity is organ-specific and requires complete Freund's adjuvant. Possible implications in experimental immunologic orchitis are discussed.