A cow's risk of acquiring a new intramammary infection during the dry period increases with milk production at drying off and decreases as mammary gland involution progresses. A method commonly used to reduce milk production is a drastic reduction in feed supply in the days that precede drying off. Milk production can also be reduced by inhibiting the lactogenic signal driven by prolactin (PRL). This study aimed to compare the effects of these 2drying-off procedures on metabolism, immunity, and mammary gland involution in cows. A total of 24Holstein cows in late lactation were assigned to 1 of 3treatments based on milk yield, somatic cell count, and parity. The cows were fed a lactation diet until drying off (control; n=8), only dry hay during the last 5d before drying off (DH; n=8), or the same lactation diet as the control cows but with twice-daily i.m. injections of 4mg of quinagolide, a specific inhibitor of PRL release, from 5d before drying off until 13d after (QN; n=8). Quinagolide induced a decrease in PRL concentration in blood and in milk and mammary secretions on all the injection days. Interestingly, PRL was also depressed in the blood and milk of the hay-fed cows before drying off. Both the QN and DH treatments induced a decrease in milk production, which averaged 17.9 and 10.1kg/d for the QN and DH cows, respectively, at drying off in comparison with 24.8kg/d for the control cows. Both BSA concentration and Na(+)-to-K(+) ratio increased faster in the mammary secretions of both the DH and QN cows than in those of the control cows, whereas citrate-to-lactoferrin ratio, another indicator of involution rate, decreased faster. The DH treatment decreased blood concentrations of glucose and most amino acids and increased blood concentrations of β-hydroxybutyrate and nonesterified fatty acids. Quinagolide increased blood glucose but did not affect the other metabolites. The serum harvested on d-1 from the hay-fed cows reduced peripheral blood mononuclear cell proliferation and IL-4 production, whereas the serum from the quinagolide-treated cows had no effect. In conclusion, this experiment shows that PRL-release inhibition could be a new alternative for reducing milk production before drying off and for hastening mammary gland involution without disturbing the metabolism of the cow.