The middle stretch of the Madeira River has supported an intensive commercial fishery for several decades. Developed in an area of rapids and waterfalls, this fishery focuses primarily on catfish stocks, mainly pimelodids. Data from fish landings collected in the years immediately prior to the start in operations of two large hydroelectric dams were used to estimate growth and mortality rates for Pirinampus pirinampu (Spix & Agassiz) and Brachyplatystoma platynemum Boulenger. In addition, stock assessment was carried out for both species, and the results used to evaluate the status of the fishery. Mean population parameters were L∞ = 80.85 cm (total length), k = 0.52 year−1, ϕ = 3.53, A0.95 = 6 year, M = 0.87, F = 1.41–1.64 and Z = 2.28–2.51 for P. pirinampu; and L∞ = 95.55 cm (total length), k = 0.28 year−1, ϕ = 3.40, winter point = 0.41, A0.95 = 11 year, M = 0.55, F = 0.16–0.35 and Z = 0.71–0.90 for B. platynemum. Yield-per-recruit analysis indicated P. pirinampu was overfished and that the stock of B. platynemum was under-exploited. Moreover, overfishing of the P. pirinampu stock and the effects of fragmentation caused by the construction of the dam should be monitored.