Existing Syrian hamster embryo (SHE) cell‐transformation assay methods were modified to allow the assay of complex synfuel mixtures. A shale oil, high‐molecular‐weight, high‐boiling distillates from two different solvent‐refined coal (SRC) processes, and two crude petroleum samples caused transformation of SHE cells. Chemical fractionation of SRC‐II heavy distillate and assay of resultant fractions allowed detection of significant transforming activity in chemical fractions, where such activity had not previously been observed. The polyaromatic‐hydrocarbon‐enriched fraction, neutral aliphatic hydrocarbon fraction, and neutral tar fraction all showed a positive response in the SHE assay. In addition, we confirmed earlier data showing that both the tar fractions (basic and neutral) and the soluble basic fractions from both SRC processes and shale oil contained genetically active materials.