Chronic mastitis in a single quarter can cause high SCC, clinical signs, or death in dairy cows. Casein hydrolysate (CH) is an intramammary infusion treatment reported to induce mammary involution. Objectives were to study cessation of milk production after CH infusion of one mastitic quarter for remaining lactation, subsequent 3-quartered cow milk production and SCC. Following the next calving, cow and quarter milk production, SCC and bacterial cure were evaluated. Criteria for study cows were: target quarter SCC >10⁶/mL, total milk SCC >500,000/mL, target quarter producing >20% (front) or >25% (rear) of cow milk, cow producing ≥22.7 kg of daily milk, 75–190 d until next due date, and mycoplasma-negative. Cows were blocked based on parity and culture status, and 3 treatments were randomized in a 2:2:1 ratio: CH, placebo (P, undigested casein), negative control (NC, stopped milking quarter only). Target quarters were milked 1× and treated for 3 d, then not milked until next calving. Total-cow milk and SCC were measured 7–14 d later. Post-calving, cow and treated quarter SCC and production were measured once, 10–21 DIM. Bacterial cure criteria: all 3 weekly cultures during the first 21 d of lactation negative for previous pathogen. Forty cows were enrolled, 12 were culled and 28 completed the study (14 CH, 9 P, 5 NC). Pretreatment measures were the same among treatment groups. Decreases in cow SCC (down by 966,000/mL) and cow production (14%) for the remainder of lactation after treatment of the target quarter were significant (P < 0.02, ANOVA), but not different among treatments. After calving, total-cow production (33.2 kg), target quarter SCC (1.41 × 10⁶/mL) and quarter production (25% of cow) were not different among treatments. The CH and NC had significant decreases in target quarter SCC after next calving (down 2.76 × 10⁶/mL and 5.32 × 10⁶/mL; P < 0.003). Cure rate (14/17, 82%) was not different among treatments, chi-squared. Casein hydrolysate infusion was associated with involution of mastitic quarters, reduced SCC, and all quarters returned to milk production following calving.