Yield and protein concentration in soybean are generally negatively correlated. The objective of our research is to assess the effectiveness of selecting for high protein among F2 plants from crosses between high-yielding and high protein parents followed by selection for high-yielding inbred lines to combine high yield and high protein. From 9 high protein F2 families selected for either high or low yield, 270 F4 lines were evaluated in 2004. To evaluate yield differences within and among F2 families, five high- and five low-yielding F4 lines were selected from each family. These lines were evaluated at three locations in Illinois in 2005 and 2006. Our initial results show that selecting for high protein among F2 plants is highly effective. The 90 F4 lines averaged 67 g kg-1 higher in protein concentration than the cultivar Dwight and some lines were higher than 100 g kg-1 . Selection for yield in the F3 generation was not effective. No differences were found among the mean yields of the F4 lines for 7 of the 9 families. However, there was significant variation for yield within all 9 families with a mean difference of 249 kg ha-1 between the high- and low-yielding selections. There was less variation for protein concentration but with significant differences for protein between the high- and low-yielding lines for 6 families and a mean difference of 10 mg g-1. The highest-yielding line was significantly lower-yielding than Dwight by 504 kg ha-1 but was significantly higher in protein by 51 g kg-1 and had a total protein production ha-1 comparable to Dwight. Nineteen F4 lines were comparable to Dwight in total protein ha-1. Selecting for high protein in very early generations followed by selection for yield may be an effective strategy for combining both high yield and high protein concentration.