Some sweet corn (Zea mays L.) hybrids and inbreds can be severely injured or killed after postemergence applications of certain P450-metabolized herbicides. Consequently, existing hybrids are regularly evaluated for tolerance to new herbicides, and new hybrids are evaluated for tolerance to existing herbicides. In 2005 and 2006, the University of Wisconsin Cooperative Extension Service coordinated 12 trials in six states in which a total of 149 sweet corn hybrids were evaluated for tolerance to three cytochrome P450-metabolized herbicides: nicosulfuron, foramsulfuron, and mesotrione. Hybrid responses differed substantially within and among locations. The objective of this study was to determine if alleles affecting herbicide sensitivity (e.g., cytochrome P450 alleles) were associated with differences in levels of injury to sweet corn hybrids in these trials. Based on responses of F2 progeny to nicosulfuron, foramsulfuron, and mesotrione, 95 hybrids were classified as homozygous for alleles conditioning herbicide tolerance; 47 hybrids were classified as heterozygous with one allele each conditioning tolerance and sensitivity; and two hybrids were classified as homozygous for alleles conditioning sensitivity. When trial mean levels of injury after applications of mesotrione, nicosulfuron, and foramsulfuron in the herbicide trials were above 1%, 4%, and 5%, respectively, the response of the three genotypic classes of hybrids followed a consistent pattern. Homozygous-sensitive hybrids were injured most severely and often were killed by the two acetolactate synththase-inhibiting herbicides, nicosulfuron and foramsulfuron. Heterozygous hybrids had an intermediate response to all three herbicides that was more similar to homozygous-tolerant hybrids than homozygous-sensitive hybrids; however, injury to heterozygous hybrids was 1.5 to 2.3 times greater and significantly (P < 0.05) different from homozygous-tolerant hybrids based on t tests of group means and comparisons of predicted values from regressions of genotypic means on trial means. Based on responses of the 149 hybrids in this trial, the potential for and level of crop injury from use of nicosulfuron, mesotrione, and foramsulfuron on any specific sweet corn hybrid is conditioned largely by alleles at a single locus.