The effect of 14 or 19 days of 10% dietary lactose administration on Salmonella enteritidis (SE) colonization and histological, morphometric, and organic acid changes of the ceca were investigated. At Day 13 or 18, chicks were challenged with 10(8) cfu of SE. Chicks were killed and cultured 24 h later. A reduction in the total number of positive SE organ invasions was observed following 14 days (P < .001) or 19 days (P < .005) of treatment in chicks fed with lactose. Histological examination revealed a marked reduction in lamina propria thickness of ceca, as well as subjective epithelial cell proliferation from chicks following either 14 or 19 days of lactose administration. Using morphometric analysis, a reduction in the mean lamina propria thickness in chickens fed with lactose during 14 or 19 days was observed as compared with controls (P < .05). Yet, an increase (P < .05) in the mean epithelial cell length in both lactose-treated groups was observed as compared with controls. Lactose decreased luminal pH (P < .05) and increased the concentration of acetic, propionic, butyric, and lactic acid (P < .05). These data indicate that lactose-induced resistance to SE organ invasion is associated not only with an increase in organic acid concentration but also with measurable morphological changes of the cecal mucosa.