Abstract: Cotton boll rot is a fungal and/or bacterial infection associated with high humidity and a lack of ventilation in the canopy during the flowering, boll development and dehiscence of cotton (Gossypium spp.). The severity of infestation can vary widely but the disease manifests itself through reduced yields and a deterioration of fiber quality. A wide variety of causal agents negates the possibility of developing direct genetic resistance but previous studies have shown that okra leaf cotton is an effective way of controlling boll rot. However, the reduced leaf area of these cultivars limits yield potential. Conversely, sub-okra cotton has minimal field resistance to boll rot but yields competitively with normal-leafed varieties. Here, an experimental open-pollination approach was used to develop hybrid lines containing both the sub-okra and okra alleles. The ability of these lines to counter boll rot was tested against parental lines, a hand-pollinated F1 and a normal-leaf control at five different locations throughout the southeastern United States. Data from the one location with sufficient boll rot showed that an open-pollinated okra X sub-okra line was just as effective at reducing boll rot as the okra leaf parent. This suggests that open-pollinated lines may be an effective means of combating boll rot that should not result in reduced yields, although the latter conclusion has yet to be confirmed.