The lipophilic extract of the cultured terrestrial blue-green alga Scytonema pseudohofmanni Bharadwaja contains five novel macrolides, scytophycins A (1), B (2), C (3), D (4), and E (5), which exhibit cytotoxicity and antifungal activity. The structures of 1-5 have been determined mainly from spectroscopic data. The relative stereochemistries of the scytophycins are based on an X-ray crystallographic analysis of a transformation product of scytophycin C (8) and comparison of the ¹H and ¹³C NMR spectra of 1-5. The absolute stereochemistries of the scytophycins have been deduced from a circular dichroism study of the β-benzoate ester 16, obtained in five steps from scytophycin B, and comparison of the CD curves of 1-5. These novel secondary metabolites appear to be biogenetically related to the marine natural products swinholide A, ulapualides A and B, and kabiramide C.