Pyrroloquinoline quinone (PQQ) is proposed as a nutritionally important growth factor, and we provide evidence that PQQ improves reproduction performance in BALB/c mice and stimulates neonatal growth. In the first experiment, weanling female BALB/c mice were adapted to a chemically-defined diet containing 0, 100, 200, 300, 1000, or 5000 ng PQQ/g of diet. The mice were bred and their reproductive performance and surviving offspring were assessed for 20-wk. Reproductive outcome was markedly compromised for the groups most deprived of PQQ. Supplemented groups (> or = 1000 ng PQQ/g diet) had 8 pups/litter compared with 4-5 pups/litter in the PQQ-deprived groups (< or = 300 ng PQQ/g diet). Of the pups surviving to weaning, 8 of 10 survived when PQQ was added to the diet (> or = 300 ng PQQ/g diet) compared with 4 of 10 in the PQQ/deficient group. The apparent requirement for PQQ for optimal growth of surviving neonates was estimated to be > or = 300 ng PQQ/g of diet. Moreover, splenic cell response to the mitogens concanavalin A and lipopolysaccharide, appeared related to PQQ intake. In a second experiment, female BALB/c mice were fed diets containing PQQ added at 0 or 1000 ng/g of diet, and interleukin 1 and 2 production were assessed. In particular, levels of interleukin 2, an autocrine and paracrine growth factor, were reduced in mice fed the deficient diet at a time when T-cell proliferation occurs in neonates. Results suggest that PQQ or similar compounds may play nutritionally important roles at critical stages in development.