The present study investigated the effects of intraperitoneal injections of thymosin alpha1 on the supraventricular amoeboid microglial cells (SAMC) in the newborn athymic and normal BALB/c mice. The microglial cells labelled by the lectin GSA I-B4 and the antibody Mac-1 showed a 27% reduction in number in the athymic mice receiving thymosin alpha1 injections compared with those receiving vehicle injections, and a 37% reduction in BALB/c mice receiving thymosin alpha1 injections compared with those receiving vehicle injections. Some of the SAMC in both BALB/c and athymic mice receiving thymosin alpha1 injections became ramified, while the remainder still exhibited their normal amoeboid appearance with few filopodial processes. Ultrastructurally, the lectin reaction product was confined to the plasma membrane and some cytoplasmic vacuoles of labelled SAMC. In both BALB/c and athymic mice, some labelled microglial cells became slender or elongated after thymosin alpha1 injections. Also their cytoplasm was reduced and contained fewer organelles. Radioimmunoassay of the plasma of thymosin alpha1 and vehicle-injected mice showed that there was a significant increase in the cortisol level in BALB/c (P < 0.01) and athymic (P < 0.001) mice 5 days after thymosin alpha1 injections, compared with that of the control mice. The results point to a strong correlation between the reduction of SAMC and the increased level of plasma cortisol. Supporting this is the fact that cortisol is known to suppress the production of monocytes considered to be the precursors of amoeboid microglia.