A two-factorial experiment was conducted in order to quantify and distinguish the influences of altitude and forage origin on metabolism and milk synthesis of dairy cows kept at Alpine locations. Each of four experimental groups comprised six dairy cows in early to mid lactation which were kept tethered in barns at altitudes of either 2000 (Alpine) or 400 m above sea level (a.s.l.) (lowland). Two groups (Alpine and lowland) received hay ad libitum, a third group kept in the lowlands was pair-fed to the Alpine group and a control group was offered silages and concentrates according to milk yield. Two hay types, with origin either from 2000 or 400 m a.s.l., were offered to all hay-alone groups following a change-over design over three 21-day periods. Transferring cows to high altitude triggered a complex adaptation process, which resulted in depressions of food intake at the beginning of the experiment and changed plasma levels of metabolic traits indicating an energy deficit. On average over the entire experiment, high altitude sojourn elevated plasma β-hydroxybutyrate and decreased plasma glucose levels. Yields of milk and of main milk constituents were not significantly affected, but milk protein content was reduced in both the Alpine and in the pair-fed group. No generally elevated maintenance requirements as a consequence of hypoxia were found. Hay-alone feeding caused a co-limitation of net energy and absorbable protein in both hay types which was almost completely compensated by a reduction of milk yield. The hay of Alpine origin had a lower digestibility and crude protein content than the lowland hay which resulted in changes in blood plasma traits and a further suppression of milk yield and milk protein and lactose contents. Due to the low N content of the Alpine hay, N utilization for milk protein synthesis remained similar to that found with lowland hay, and manure N of these cows contained the lowest proportion of easily-volatile urine N. In conclusion, forage origin in conjunction with diet type seems to explain the major part of the adverse effects that the Alpine sojourn exerts on lactating dairy cows while the effects of hypoxia appear to be of lesser importance.