Three new tetramic acid derivatives, epicoccamides B-D, together with the known epicoccamide, were isolated from an Epicoccum sp. associated with the tree fungus Pholiota squarrosa. The structures of the new compounds were elucidated on the basis of their physical data and chemical degradation. The epicoccamides differ in substitution pattern and in the size of the central carbon chain. The derivative with the longest chain, epicoccamide D, induces morphogenesis and pigment formation in surface cultures of the fungus Phoma destructiva at a concentration of 1.7 mM. Moreover, it exhibits weak to moderate cytotoxicity to HeLa cell lines (CC50 17.0 microM) and antiproliferative effects toward mouse fibroplast (L-929) and human leukemia cell lines (K-562) with growth inhibition (GI50) of 50.5 and 33.3 microM, respectively.