Human mesangial cells (HMC) were analyzed for their expression of 20-kDa homologous restriction factor (CD59), a glycophospholipid-anchored regulatory protein of the complement cascade. Flow cytometric analysis showed that CD59 was expressed on the HMC membrane and, following the activation of the terminal pathway complement components, CD59 expression on the HMC membrane increased. Northern blot analysis showed that CD59 mRNA levels increased by complement activation. Of interest, CD59 mRNA levels increased by soluble complement activation product, zymosan-activated C8-depleted serum, but not zymosan-activated C5-depleted serum. This effect of soluble complement activation product was due to the presence of the action of C5a. Thus, recombinant C5a increased CD59 mRNA levels. The capacity of CD59 to reinsert into rat E and inhibit C-mediated lysis was inhibited by mAb against CD59 (1F5). Metabolic labeling using [35S]cysteine showed that the molecular mass of CD59 in HMC was 20 kDa. In conclusion, CD59 is present on HMC and the expression of CD59 is controlled by at least two steps of complement activation pathway, C5 and C8.