Weed population estimates were collected from four Glycine max fields during the summers of 1997 and 1998. Seedling weed populations were sampled using a regular coordinate system on a grid either 50 by 50, 30 by 30, or 10 by 10 m. MSU-HERB and Mississippi Herbicide Application Decision Support System (HADSS) (yield loss prediction and herbicide recommendation models for G. max) were used to determine the estimated net gain resulting from simulated herbicide applications at each sample location in each field. When necessary, the appropriate data points from the 10- by 10-m grid were removed to form population data sets on grids 20 by 20, 40 by 40, and 80 by 80 m. The objectives of this research were to compare estimated economic returns of site-specific herbicide management and broadcast herbicide management in nontransgenic and glyphosate-tolerant G. max and to evaluate the effects of various weed sampling intensities on estimated economic returns from site-specific herbicide applications. Site-specific herbicide management was the compilation of simulated herbicide treatments giving the highest estimated net gains at each location within each field. Broadcast herbicide management was the simulated broadcast application giving the highest estimated net gain for each field. Sampling costs and the unattainable site-specific application costs were not included in the estimated net gain calculations. In nontransgenic G. max production, the estimated net gain for treating the four fields with site-specific technology was $104.76 ha−1 higher than when using the optimum broadcast herbicide. In glyphosate-tolerant G. max production, the average estimated net gain for site-specific treatment of the fields was $96.24 ha−1 higher than for treatment with the best broadcast herbicide application. In nontransgenic G. max, the estimated net gain resulting from site-specific applications on a 10-m grid was $77.17 ha−1 higher than from site-specific applications on a 20-m grid; however, in glyphosate-tolerant G. max, this difference was only $19.84 ha−1. Increased estimated net gain resulted primarily from the use of herbicides that maximized return for each field area and from the decrease of unnecessary herbicide applications because of below-threshold weed infestations.