A series of synthetic spongiane-type diterpenes have been tested in vitro for their potential antitumor and antiherpetic activity. Although the antiviral activity of these compounds against herpes simplex virus type 2 (HSV-2) was very weak, some compounds exhibited relevant cytotoxicity in the human tumor cell lines HeLa and HEp-2. The biological activity of formyl spongianes is reported for the first time. With the present study, some structure-activity trends are suggested for the cytotoxic activity of these sponge-derived natural products.