Quantitative studies were undertaken, with the small-plaque polyoma mutant SP2 and the large-plaque virus BP5, on the lytic interaction in mouse and hamster cells and on transformation of hamster cells under various conditions. In the study on the lytic interaction, one-step growth curves of the two viruses showed a higher total virus yield per culture for SP2 than for BP5. The higher total virus yield with SP2 was explained by a higher percentage of virus-yielding cells. The percentage of such cells was 3.8 to 7.0 times higher than with BP5 after inoculation of mouse cultures, and 4.2 to 20.0 times higher after inoculation of hamster cultures. There was a similar average virus yield per virus-yielding cell [2 to 4 × 10 3 plaque-forming units (PFU)] with both viruses. No effect was found on the plaque size of SP2 on mouse embryo monolayers after addition of DEAE-dextran or protamine to the agar nutrient overlay. In the study on cell transformation, the percentage of transformed clones (PTC) was determined by cloning cultures of hamster cells after exposure to either virus. After exposure of cultures grown at 37° at a virus: cell ratio of 20 PFU per cell, the PTC was 0.1%–0.4% for BP5, and 0.8%–2.0% for SP2. This showed a 4.0–14.0 times higher PTC for SP2. The increased efficiency of SP2 with respect to PTC was thus of about the same order of magnitude as the increased efficiency of SP2 in the lytic interaction. Similar differences in the PTC of the two viruses, as compared with those obtained after a single exposure at 20 PFU per cell, were found after a single exposure at a virus: cell ratio of 1000 PFU per cell, and after three successive exposures at 10 PFU per cell at 24-hour intervals. Exposure at 1000 PFU did not appreciably increase the PTC, and even after the three successive exposures, the highest PTC was still only 3.0% for SP2 and 0.4% for BP5. The PTC could, however, be increased to 10.0% for SP2 and to 3.0% for BP5, by maintaining cultures at 24° before cloning, with virus exposure either at the beginning or at the end of the period at 24°. The results thus indicate that the use of a virus mutant, and differences in the culture conditions, can change the rate of polyoma-induced cell transformation.