Cell transformation assays (CTA) detect phenotypic changes associated with neoplastic transformation and available evidence suggests in vitro cell transformation may stimulate early components of the multistage process of carcinogenesis. Moreover, CTAs may aid in identifying potentially non-genotoxic carcinogens that may not be detected by conventional genotoxicity assays. We have tested whether total particulate matter (TPM) and cigarette smoke condensate (CSC) generated from Kentucky reference 3R4F cigarettes induce morphological transformation using three versions of the CTA:the Syrian Hamster Embryo (SHE) cell transformation assay using a 24-hour and 7-day exposure protocol, the SHE assay using an initiator/promotor protocol, and an initiator/promotor assay using Bhas 42 cells (v-Ha-ras-transfected Balb/c 3T3 cells). Both TPM and CSC were positive in the SHE 7-day exposure with 12.5- and 9-fold increases, respectively, in the number of morphologically transformed colonies as compared to solvent controls, CSC was positive (2.7-fold increase) while TPM was equivocal in the SHE 24-hour exposure assay. TPM and CSC each induced positive responses in the SHE initiator and promotor assays with approximately 3-fold increases in the number of morphologically transformed colonies. In the Bhas 42 initiator assay, TPM produced a positive response (3.5-fold increase) while CSC was equivocal, however, in the Bhas 42 promotor assay both TPM and CSC were positive, inducing approximately a 12-fold increase in morphologically transformed foci. Among the CTA models investigated, the Bhas 42 promotor assay provided the most linear responses coupled with a robust increase in transformed foci across the treatment range and may therefore be a useful technique to evaluate cigarette samples.