Two experiments were conducted to determine whether 3 different clays in the nursery diet reduce diarrhea of weaned pigs experimentally infected with a pathogenic Escherichia coli. Weaned pigs (21 d old) were housed in individual pens of disease containment chambers for 16 d [4 d before and 12 d after the first challenge (d 0)]. The treatments were in a factorial arrangement: 1) with or without an E. coli challenge (F-18 E. coli strain; heat-labile, heat-stable, and Shiga-like toxins; 10(10) cfu/3 mL oral dose daily for 3 d from d 0) and 2) dietary treatments. The ADG, ADFI, and G:F were measured for each interval (d 0 to 6, 6 to 12, and 0 to 12). Diarrhea score (DS; 1 = normal; 5 = watery diarrhea) was recorded for each pig daily. Feces were collected on d 0, 3, 6, 9, and 12 and plated on blood agar to differentiate β-hemolytic coliforms (HC) from total coliforms (TC) and on MacConkey agar to verify E. coli. Their populations on blood agar were assessed visually using a score (0 = no growth; 8 = very heavy bacterial growth) and expressed as a ratio of HC to TC scores (RHT). Blood was collected on d 0, 6, and 12 to measure total and differential white blood cell (WBC) counts, packed cell volume (PCV), and total protein (TP). In Exp. 1 (8 treatments; 6 replicates), 48 pigs (6.9 ± 1.0 kg of BW) and 4 diets [a nursery control diet (CON), CON + 0.3% smectite (SM), CON + 0.6% SM, and CON until d 0 and then CON + 0.3% SM] were used. The SM treatments did not affect growth rate of the pigs for the overall period. In the E. coli challenged group, the SM treatments reduced DS for the overall period (1.77 vs. 2.01; P < 0.05) and RHT on d 6 (0.60 vs. 0.87; P < 0.05) and d 9 (0.14 vs. 0.28; P = 0.083), and altered differential WBC on d 6 (neutrophils, 48 vs. 39%, P = 0.092; lymphocytes, 49 vs. 58%, P = 0.082) compared with the CON treatment. In Exp. 2 (16 treatments; 8 replicates), 128 pigs (6.7 ± 0.8 kg of BW) and 8 diets [CON and 7 clay treatments (CON + 0.3% SM, kaolinite, and zeolite individually and all possible combinations to total 0.3% of the diet)] were used. The clay treatments did not affect growth rate of the pigs. In the E. coli challenged group, the clay treatments reduced DS for the overall period (1.63 vs. 3.00; P < 0.05), RHT on d 9 (0.32 vs. 0.76; P < 0.05) and d 12 (0.13 vs. 0.39; P = 0.094), and total WBC on d 6 (15.2 vs. 17.7 × 10(3)/μL; P = 0.069) compared with the control treatment. In conclusion, dietary clays alleviated diarrhea of weaned pigs.