A cross-sectional study employing two-stage cluster sampling was conducted between December 2005 and March 2006 to compare adults' knowledge of HIV/AIDS voluntary counseling and testing (VCT) and the attitudes toward and acceptance of VCT between a county in which a comprehensive HIV/AIDS program, China CARES (CC), was available, and a county where it was not. Information on HIV/AIDS knowledge, awareness of VCT, and attitudes was collected. All participants were given a coupon for free VCT after the cross-sectional interview. Uptake of VCT was measured within 2 months of the interview. More participants in the CC county knew someone infected with HIV, had participated in AIDS-related activities, and/or had heard about China CARES. In the control county, education and income levels were higher, there were fewer minorities, and there was a higher proportion of women. VCT uptake was low. Overall, no significant differences in uptake were found between the two counties. Urban residents of the CC county had higher HIV/AIDS knowledge levels than urban residents of the comparison county (p = 0.002). Residents of the CC county were more discriminative against HIV/AIDS and persons living with HIV/AIDS (PLWHA) and had lower perceptions of risk. The differences may be due to the higher proportion of rural residents in the CC county (p < 0.001). The China CARES program may have had a positive effect on urban areas of Guizhou Province in terms of improving HIV/AIDS and VCT knowledge and reducing discrimination, but had little impact in the rural areas. If the China CARES program is to be successful, it must implement a more effective education program and increase the acceptability of testing.