This study compares the trends in AIDS case reports in Southern states and in other regions and estimates the factors associated with the trends. Data from the HIV/AIDS Surveillance Reports 1999 and 2004 of the Centers for Disease Control and Prevention were used to calculate the proportion of the total cumulative cases (1981-2004) that occurred in the five most recent years (2000-2004). A linear regression model was fitted to estimate the factors associated with the highest recent growth rate for AIDS cases by state. Results revealed that Southern states (including the District of Columbia) are more likely to have a disproportionate proportion of total AIDS cases reported within the past five years (25.5% in 16 states and the District) compared to the rest of the U.S. (mean = 19.3% in 34 states and Puerto Rico and the U.S. Virgin Islands; p < 0.001). Being a southern state (4.3% higher in proportion; 95% CI, 1.3%-7.3%) and higher representation of black race (0.1%, 95% CI, 0.02%-0.2%) were factor independently associated with higher recent growth rate for a state. AIDS case rates suggest recent worrisome trends in the South. Those states and territories that are in the South and that have higher proportions of African-Americans have a higher proportion of recent AIDS case reports than elsewhere, suggesting the need for a special geographic focus to encourage prevention, HIV testing, and access to care.