An experimental model was developed in the dog in which a renal allograft was placed in the neck, leaving 1 of the dog''s own kidneys in situ. Five nonimmunosuppressed pairs of dogs were studied by using the leukocyte migration test (LMT) as an in vitro measure of cell-mediated immunity. Antigen preparations from leukocytes, kidney, liver and skeletal muscle from the kidney donor and the recipient were used in the LMT to study responses against transplantation and organ-specific antigens. Inhibition of migration with donor-specific leukocyte and kidney antigens was detectable prior to clinical evidence of rejection, which was confirmed histologically. Concurrently, inhibition was observed with autologous kidney antigen and histological damage was noted in the recipient''s own nontransplanted kidney, accompanied by increasing proteinuria. Autologous serum withdrawn daily and added to the test culture medium abolished the inhibition of migration, suggesting the development of blocking factor.