Path analysis was used to model the direct and indirect relationships among age, previous lactation yield or estimated transmitting ability for milk, body weight, days dry, reproductive disorders, milk fever, mastitis, reproductive performance, current milk yield, and culling. Prospective data were from 784 primiparous and 2,066 multiparous Holstein lactations from 33 herds. Heifers that were older, of lighter weight, or who had lower estimated transmitting ability for milk had more problems, less milk, and poorer survival. Dystocia in heifers had several detrimental consequences including 2.9 to 4 times more retained placenta, metritis, and culling and +7.4 d more to first service. Cystic ovaries were associated directly with 376 kg greater milk yield and with a 16.5-d delay in first service. Failure to conceive at first service and mastitis increased risk of culling 5.2 to 10 times. In multiparous cows, milk fever increased risk of reproductive disorders by 1.6 to 4.2 times and indirectly contributed to poor breeding performance and increased culling. Risk of culling was increased 2.1 to 3.7 times directly by mastitis and dystocia and by poor breeding performance.