Two novel indole-tetramic acid alkaloids-griseofamine A (1) and griseofamine B (2)-and (R)-N-(2-methylbutanoyl)-L-tryptophan (3), were isolated from the fungus Penicillium griseofulvum. Compounds 1 and 2 feature a 6/5/6/5 and 6/5/7/5 tetracyclic ring systems formed by the fusion of an indole unit and a tetramic acid via a six or seven-membered N-heterocyclic ring, respectively. The plausible biosynthetic pathways of 1-3 are proposed. Compound 1 shows a weak anti-inflammatory activity by inhibition of NO and TNF-alpha production.