The rate constants for internalization and subsequent extrusion of acetylcholine receptors (AChRs) during degradation in adult innervated and denervated mouse diaphragm muscles were determined using proteinase K (PK) digestion. This procedure separated 125 I-β£-bungarotoxin (Bgt)-labeled AChRs into PK-sensitive and PK-resistant compartments. The time course of the residual radioactivity in these two compartments suggested that they represented surface membrane and internalized compartments, respectively. The data were compatible with a mathematical model based on the assumption that during degradation of AChRs a surface compartment, A, fed an internal compartment, B, with an internalization rate constant (k i ), and that B is drained from the cell with an extrusion rate constant (k o ). Using the mathematical model, we were able to determine that k i and k o were, respectively, 0.068 (t 1/2 Ο³ 10.2 days) and 0.69 -0.55 (t 1/2 Ο³ 1.0 - 1.25 days) for innervated muscle and were, respectively, 0.69 (t 1/2 Ο³ 1.0 day) and 6.93 (t 1/2 Ο³ 0.1day) for denervated muscle. Thus, the rate for internalization was about 8 -10 times slower than that for extrusion from the cell for both the slowly degrading innervated (Rs) AChRs and for the rapidly degrading denervated (Rr) AChRs. This inequality betweeen k i and k o therefore allows the combined quantity of A(t) Ο© B(t) , usually measured in AChR degradation studies, to approximate a single exponential.