Four of the five runner-type peanut, Arachis hypogaea L., cultivars currently being grown in the Southeastern United States have significantly larger seed size than the previous standard cultivar, ‘Georgia Green’. Seed count for these four cultivars averages approximately 630 seed per pound, compared to 850 seed per pound for Georgia Green. Two primary concerns with peanut cultivars with significantly larger seed size are response to non-irrigated production and calcium requirement. Research trials were conducted in crop years 2009-2011 to determine the response of the four large-seeded cultivars to rain-fed production and to variable rates of calcium sulfate. Trials were conducted at University of Georgia research centers and on producers’ fields. The hypothesis was that the large-seeded cultivars would respond with lower yield under rain-fed conditions and would require higher rates of calcium sulfate compared to the small-seeded Georgia Green. Results indicated that the large-seeded cultivars had higher yields under non-irrigated production, primarily due to genetically higher yield potential. Research also indicated the larger-seeded cultivars had the same calcium sulfate requirement as Georgia Green.