The effect of graded doses of irradiation (cobalt-60) on the morphology of McCoy cells was analyzed, and 4,000 to 5,000 r was selected as a satisfactory dose for production of giant cells. The susceptibility of radiation-induced giant cells to chlamydial infection was compared with that of nonirradiated cells by using three strains of Chlamydia trachomatis and one of C. psittaci. Monolayers of giant cells were more susceptible than normal McCoy cells as indicated by (i) greater numbers of inclusions (four- to eightfold) per unit area of monolayer, (ii) larger inclusions (fourfold greater in area), (iii) higher infective titers (1 log or more greater) of harvested cells, and (iv) greater ease of promoting a second cycle of growth. Graded doses of irradiation were applied also to mouse fibroblast (L) cells, and a similar increase in susceptibility to chlamydial infection was noted. It is concluded that giant cells produced by irradiation possess advantages over nonirradiated cells in culture for growth of Chlamydia.