Objective.-To determine the in vitro sensitivity of 4 vaccine-associated feline sarcoma (VAFS) cell lines to the chemotherapeutic agents vincristine and paclitaxel. Sample Population.-Cell lines derived from 4 VAFS specimens. Procedures.-Cell lines were cultured in vitro and individually exposed to various concentrations of vincristine and paclitaxel. Survival was estimated after 24 and 72 hours of exposure to each drug, and the drug concentrations that resulted in 50 and 90% reduction in number of viable cells (IC50 and IC90, respectively) were calculated. Results.-Both vincristine and paclitaxel had significant dose-dependent effects on the viability of the VAFS cell lines. After 72 hours of drug exposure, the IC50 and IC90 of vincristine for the 4 cell lines were between 0.005 to 0.039 μg/ml and 0.045 to 1.027 μg/ml, respectively. The IC50 and IC90 values for paclitaxel were between 0.037 to 0.092 μg/ml and 2.450 to 15.413 μg/ml, respectively. Conclusions.-Results of pharmacokinetic studies on vincristine and paclitaxel in other species suggest that concentrations greater than the IC50 values may be possible for both drugs in feline patients as well. The drug concentrations at which viable cell numbers were reduced by 90% may also be attained in vivo for some cases, but detailed information is needed regarding the distribution, concentration, duration of availability, and toxicity of various drugs in cats. Carefully chosen combinations of antineoplastic agents need to be screened to identify treatment protocols that may be further evaluated clinically for the treatment of VAFS.