Objective: To de®ne the cellular basis for immune enhancement by a probiotic lactic acid bacteria strain (Bi®dobacterium lactis HN019); and to determine whether immune enhancement can be optimized by delivery in oligosaccharide-enriched low-fat milk. Design: A double-blind, three-stage before-and-after intervention trial. Setting: Taipei Medical College Hospital, Taipei, Taiwan. Subjects: Fifty healthy Taiwanese citizens (age range 41 ± 81; median 60) randomly allocated to two groups. Interventions: In stage 1 (run-in control stage) all subjects consumed reconstituted low-fat milk (LFM) for 3 weeks; in stage 2 (probiotic intervention) subjects consumed B. lactis in LFM (group A) or B. lactis in lactosehydrolysed LFM (group B) for 3 weeks; in stage 3 all subjects returned to non-supplemented LFM for a further 3 weeks (washout stage). The innate immune functions of two different leucocyte types (polymorphonuclear (PMN) cells and natural killer (NK) cells) were assessed at four time points via in vitro analyses on peripheral blood samples. Results: While consumption of LFM alone had no signi®cant effect on immune responses, stage 2 results indicated signi®cantly enhanced PMN cell phagocytosis and NK cell tumour killing activity following consumption of milk containing B. lactis. These increases levelled off following cessation of B. lactis consumption, but remained above the pre-treatment values. Increases in PMN and NK cell activity were greatest among subjects who consumed B. lactis in lactose-hydrolysed LFM. Conclusions: Dietary consumption of the probiotic bacterium B. lactis HN019 enhanced immune function of two different types of leucocytes; the degree of enhancement was increased by consuming B. lactis in an oligosaccharide-rich substrate. Sponsorship: Financial support was provided by the New Zealand Dairy Board.