Cell-mediated immunity in lepromatous leprosy patients with and without amyloidosis has been studied. Amyloidosis occurred mostly in patients with a history of recurrent erythema nodosum leprosum (ENL) reactions. For this reason, two control groups of leprosy patients were included, one having a history of recurrent ENL and the other little or no ENL. The lack of responsiveness to lepromin in vivo and in vitro, characteristic of lepromatous leprosy, was not altered by the presence of amyloidosis or a history of ENL. No significant difference between the patient groups was observed in the response to PPD in vitro, but skin reactivity to PPD was significantly lower in the patients with amyloidosis than in those without amyloidosis. In contrast, the PHA responses of patients with amyloidosis were significantly higher than those of control patients without a history of ENL, but not significantly different from those of control patients with a history of recurrent ENL. Lepromatous leprosy patients who develop amyloidosis thus appear to belong to a group, susceptible to repeated attacks of ENL, whose PHA responses are higher than those of other lepromatous leprosy patients. The lower skin reactivity to PPD observed in the amyloid group may reflect a general impairment in delayed cutaneous hypersensitivity.