Inward rectification of a calcium-activated K+ channel in neurons cultured from the hypothalamus and brain stem of 1-day-old rats was studied by using patch-clamp techniques. A big conductance calcium-activated K+ channel with a slow gating rate was observed in inside-out patches. With symmetrical K+ across patches, inward conductance of this calcium-activated K+ channel was 216 +/- 14 (SE) pS (n = 4 patches), which changed little as different [Ca2+] was included in the bath solution. Outward conductance of this calcium-activated K+ channel was regulated by [Ca2+] in the bath solution and was 74 +/- 15 pS with 500 microM Ca2+. The higher level of Ca2+ on the intracellular side of the membrane caused the larger degree of rectification. Mg2+ only had a minor effect on rectification of this calcium-activated K+ channel.