Potential clinical and hematologic complications were studied in 18 baboons subjected to cross circulation for periods of five to 31 days. Cross circulation was a safe procedure during the first four days. After that time, anaphylactoid reactions potentially fatal for one or both partners, thrombocytopenia, leukopenia, hemolytic anemia, and in one case, marrow depression were seen. These reactions were ameliorated but not entirely controlled by administration of methotrexate. When cross circulation was discontinued after five to 31 days, eight of nine baboons showed prompt clinical and hematologic recovery without late sequelae.