Sixty-eight (Experiment 1, 46 days feeding) and sixteen (Experiment 2, 21 days feeding) 21-days-old weaned pigs were allotted to four dietary treatments including control, 0.6% organic acids (OA), 0.1% nucleotides (NA) and 0.6% OA plus 0.1% NA for determining the dietary effects. In Experiment 1, OA enhanced peripheral blood mononuclear cells proliferation on day 28 and 46. The plasma immunoglobulin (Ig) A level was elevated by OA (p < 0.06) and NA (p < 0.07), respectively. In Experiment 2, NA increased plasma IgM level, and had an interactive effect with OA on ileal Peyer's patches and mesenteric lymph node lymphocyte proliferation, bile and plasma IgA levels, and jejunal crypt depth. NA elevated gastric pepsin and jejunal alkaline phosphatase activities, however, decreased ileal aminopeptidase N, sucrase or maltase activity. These results suggest that OA and NA have synergistically enhanced the gut-associated lymphocyte responses and NA modulates the digestive tract development of weaned pigs.