Sixty-five soybean,Glycine max (L.) Merrill, breeding lines containing ‘IAC-100′ in their pedigrees were evaluated for their resistance to lepidopteran defoliation in replicated field trials during 2001–2005. Three soybean cultivars, IAC-100 (with resistance to stink bug [Hemiptera: Pentatomidae] feeding), ‘Dillon’, and ‘Hutcheson’, also were included in the evaluations. The percentage defoliation among these 68 entries ranged from 4.3 to 28.3% in 2001 and from 35.0 to 99.0% in 2002. Lepidopteran caterpillars, primarilyAnticarsia gemmatalis Hübner, but also somePseudoplusia includens (Walker) andHypena scabra (F.), peaked at 14.3 per row-meter on 11 September 2001 and at 39.7 per row-meter on 22 August 2002. Twenty-six entries with better resistance potential, plus two cultivars, were selected for continued evaluations in 2003 and 2004. Defoliation ranged from 23.3 to 56.7% among the 28 entries in 2003 and from 16.3 to 42.5% in 2004, with peak caterpillar densities of 20.3 per row-meter on 17 September 2003 and 14.5 per row-meter on 8 September 2004. From these differential responses, 12 entries were included for advanced resistance evaluations in 2005. The breeding line entries 52 (IAC-100 × V89-1301), 23 (IAC-100 × V89-1301), and 14 (IAC-100 × V71-370), plus entry 37 (IAC-100) had lower defoliation rankings during all 5 yr of this study, with the entry having the lowest defoliation ranked 1 and the entry with highest defoliation ranked either 68, 28, or 12, based on the number of entries evaluated each year. The overall mean rankings of these four entries over the 5 yr of this study were 4.4, 3.0, 4.2, and 4.6, respectively. A fifth entry, 30 (IAC-100 × V71-370), was in the top group with lower defoliation in 4 yr of this 5-yr study, and it had an overall mean ranking of 5.6. A sixth entry, 35 (Hutcheson × IAC-100), had moderate resistance (overall ranking of 19.2) compared with the standard Hutcheson (30.8 ranking of a possible highest ranking of 40.8). Entry 35 also yielded as well as the standard cultivars evaluated in the study. These lines will provide excellent sources for future soybean germplasm and varietal resistance development.