Isolated cultured murine brain macrophages (BM) were treated with supernatants of enriched astrocytic cultures. The astrocyte-conditioned medium (ACM) induced ramification of BM. In parallel, BM expressed voltage-gated outward K+ currents (I(K)) during the first 2 days after the application of ACM. However, in ramified BM which were treated once with ACM, I(K) disappeared 5 days after that treatment. In contrast, BM expressed I(K) over a period of more than 5 days when cells were treated daily with ACM. A blockade of I(K) by charybdotoxin or by kaliotoxin did not inhibit ramification of the cells. Furthermore, after application of low-concentrated ACM BM exhibited I(K) but did not change their morphology. It is suggested that in murine BM the ramification and the expression of I(K) are induced by distinct soluble factors derived from astrocytes.