N6,O2′-dibutyryl 3′,5′-adenosine monophosphate (dbc-AMP) altered morphology and growth properties of fibroblasts. During treatment with dbc-AMP, the cell body and processes were elongated, and the cells spread out and occupied a greater area in contact with the substratum. In one cell line, which normally showed extensive vacuolization, dbc-AMP greatly decreased the vacuole content. Morphologic changes were observed with all cell lines tested, including Swiss/3T3, BALB/3T3, and Swiss/3T3 and BALB/3T3 cells transformed by polyoma virus, murine leukemia and sarcoma viruses, and simian virus 40 (SV40). Usually, the changes in the SV40-transformed cells were not as extensive as those observed with the others. Also, L-2071 cells, a line that grows on a chemically defined, protein-free medium, and BHK-21 cells were responsive. Dibutyryl cyclic AMP decreased the growth rate of the cells; the effect was potentiated by theophylline. The treatment decreased by seven-fold the saturation density of 3T3 cells, a line normally displaying contact inhibition of growth at a relatively low cell density. But dbc-AMP even with theophylline did not markedly decrease the saturation density of the non-contact-inhibited transformed cells.