Milk urea content is receiving growing interest from science and industry as a tool to infer the protein adequacy of dairy cows' diets, nitrogen excretion and its environmental impact, and efficiency of animals' protein metabolism. Fourier-transform infrared (FTIR) prediction is a high-throughput method for rapidly and cheaply evaluating milk urea content at the population level. Existing knowledge of the major sources of variation (e.g., year, season, farming system, individual herd, and the cow's breed, parity, stage of lactation, and productive potential) is fragmentary. The objective of this work was to study at the population level the simultaneous effects of all the major sources of variation and their most important interactions. Milk urea content in 1,759,706 test day milk samples collected from 291,129 lactations of 115,819 cows from 6,430 herds over 8 yr was predicted by FTIR. The milk urea content data (and also milk protein percentage, for comparison) were analyzed using a linear model that included the effects of parity, days in milk (DIM) class, year, month, herd intensiveness level, cow productivity level, breed, and herd intensiveness and cow productivity levels within breed. All sources of variation of milk urea content proved highly significant, the most important in terms of F-value being breed > year > herd intensiveness level > parity. The ranking for milk protein was very different (DIM class > herd intensiveness level > parity > breed). The patterns of the least squares means for urea and protein contents of milk were also very different and sometimes contrasting. The seasonal variation in urea was sinusoidal. Urea content increased during the first 4 mo of lactation and then remained almost stable before decreasing after 11 mo. Specialized dairy breeds had lower average milk urea content than dual-purpose breeds; in the former case it was lower in Holsteins than in Brown Swiss, and in the latter it was lower in Simmentals than in Alpine Greys. The effect of herd intensiveness level was much stronger than the effect of cow productivity level; the increase in milk urea with increasing herd average daily milk yield was almost linear in the case of dairy breeds but curvilinear in dual-purpose breeds. The large differences in breed and the modest relationships with the cow's productive potential require further analysis at the genetic level to obtain information of potential use in genetic improvement of the dairy cow populations.