Abstract: Two functional parameters evaluated by NBT dye reduction and YC rosette formation and a morphological change assessed by Wright-Giemsa stain of HL-60 cells were used to determine the extent of HL-60 cell differentiation induced by retinoids and DMSO. Studies revealed that under the action of retinoic acid(RA) and its two new synthetic analogs, 4-(ethoxycarbophenyl) retiamide(RI) and 4-(hydroxycarbophenyl) retiamide (RII), HL-60 cells could be induced to differentiate to more mature cells with functional characteristics of granuloeytes. When HL-60 cells were incubated with 10^-6M of RⅠ and RⅡ for 6 days, 42.3% and 43.6% of the eells were capable of reducing NBT; 20.7% and 14.9% could form YC rosettes with yeast ceils covered by human C₃ complement. DMSO was also shown to be active in the induction of both functional differentiation phenotypes. However, the expression of C₃ complement receptor was much earlier than the emergence of NBT reduction capacity under its induction. It is resonable to speculate that the induction machanism of retinoids and DMSO is somewhat different. Both retinoids and DMSO could induce HL-60 cells into morphologically more mature myeloid cells including myeloeytes, metamyelocytes and banded neutrophils. However, only a few cells matured into fully segmented ones. The induction of differentiation of HL-60 cells by all of the drugs tested was found to be associated with a reduction of the number of viable ceils. Since this phenomenon appeared later than cell differentiation, it may be related with the change of growth characteristics of differentiated cells.