Extension of neuronal processes is fundamental for the establishment of the intricate network of the nervous system. The rat PC12 pheochromocytoma cell line is a well-known model system for the study of neuronal differentiation. In the present study the effect of a high-voltage-activated calcium channel blocker, nifedipine, on the cell differentiation was investigated. In cells cultured in a modified medium containing nifedipine (at 2.5 microM or 5.0 microM) a decrease of mitotic activity took place on the third day of culturing. An increase of total length and number of processes occurred on the fifth day. A higher concentration of nifedipine (10.0 microM) considerably suppressed vital functions of the cells. Retraction of processes together with blocking of proliferation activity was observed. In parallel with these changes, a reduction of [Ca2+]i from 100 +/- 6 nM to 50 +/- 2 nM was detected on the second day of cultivation in 2.5 microM and 5.0 microM nifedipine containing medium. At 10.0 microM concentration of nifedipine in the medium a decrease in [Ca2+]i was observed on the first day only (to 76 +/- 8 nM); then the level of free calcium concentration rose dramatically. The data obtained allow us to suggest that the decrease of [Ca2+]i during first two days of PC12 cells culturing in a nifedipine-containing medium could be a factor which stimulated their morphological differentiation.