The effects of cyclosporin A on primary and secondary infection of mice with Listeria monocytogenes was studied both at the microbiological and the histomorphological level. This drug, when given in a dose of 100 mg/kg/day, was found to inhibit the development of protective immunity after primary infection as well as the expression of acquired immunity to challenge infection as determined by counting of bacterial numbers in the spleen. The manifestation of delayed type hypersensitivity was also impaired. When the cellular immune system was functionally intact, the formation of granulomas composed of macrophages and lymphocytes enabled the animals to overcome the Listeria infection. In mice treated with cyclosporin A protective granulomatous reaction during secondary infection did not occur. Instead numerous necropurulent lesions developed in the reticuloendothelial organs, such as spleen and liver, of animals unable to control the lethal infection.