Effects of chloroquine diphosphate on fibroblasts, Yoshida sarcoma cells, Ehrlich ascites tumor cells and human neutrophils were investigated morphologically by phase contrast microscopy and cytochemical methods. The following results were obtained. 1) Fibroblasts: The fibroblasts obtained from mice previously administered with 25 mg of chloroquine diphosphate per kilogram body weight for five days showed increase of vacuoles and fat droplets in the cytoplasm. The cultured fibroblasts displayed increase of intracytoplasmic fatdroplets by addition of such small amount of chloroquine diphosphate as 2γ per 100 ml to the culture medium. As the concentration of chloroquine became high, increase in size and number of the intracytoplasmic lipid droplets and vacuoles and fragmentation of the mitochondria were observed. 2) The main morphological changes of Yoshida sarcoma cells and Ehrlich ascites tumor cells were increased of intracytoplasmic vacuoles and lipid droplets both in in vivo and in vitro chloroquine treatment. However, these changes of tumor cells were considerably mild when compated with those of fibroblasts which underwent the same treatment. 3) By the treatment of chloroquine, Yoshida sarcoma cells and Ehrlich ascites tumor cells disclosed a slight incrcase of the granules positive in PAS staining. 4) When treated with chloroquine, fat granules of Yoshida sarcoma cells and Ehrlich ascites tumor cells were observed to be increased in size and number in lipid staining. 5) Numerous granules were observed in neutrophils of patients who were administered with chloroquine disphosphate for a long period. However, patien's tumor cells showed no morphological changes. 6) In summary, chloroquine diphosphate can exert mosphological alteration on various cells which was considered to be non-specific cellular degeneration.