Ecophys.Fish is a deterministic STELLA® model for simulating rates of fish growth in environmental regimes that have simultaneous temporal variation in food, oxygen, temperature, pH, and salinity. The purpose of this article is to introduce Ecophys.Fish to those who might want to use it as a framework or starting point for applications of their own. We believe our model, although focused in autecology, will prove useful at organizational levels both below and above the individual fish. Ecophys.Fish is a quantitatively explicit interpretation of concepts originally formalized by F.E.J. Fry, almost 60 years ago. Fry's “physiological classification of environment” and his concept of “metabolic scope for activity” were coupled with conventional bioenergetics to provide the model's theoretical basis. The model's inputs are initial size of fish, and time series of temperature, pH, dissolved-oxygen concentration (DO), salinity, and food availability and its energy content. Outputs are food consumption, oxygen consumption, waste production, energy content of fish biomass, and growth. Indirectly, the output is a measure of relative fitness of the fish-environment system to support fish growth. Two variants of the model represent the euryhaline red drum (Sciaenops ocellatus) and the freshwater bluegill (Lepomis macrochirus). Ecophys.Fish had its beginnings in laboratory experiments with juvenile red drum. These experiments enabled definition of functions and their parameterization, leading to a working model that effectively simulated growth of red drum in various pond and estuary trials with caged fish. Subsequently, Ecophys.Fish was converted to simulate growth rates of caged bluegill involved in stream ecoassays. The latter work confirmed the model's generality and the utility of automated routine respirometry for empirically estimating a key model parameter. Ecophys.Fish comprises an effective tool for resolving sources of variation in fish growth, even in natural systems with high levels of environmental variability. Moreover, the model has utility for probing biological and ecological mechanisms underlying fish growth and production. Finally, Ecophys.Fish is capable of producing rich hypotheses, e.g., 1) the optimum temperature for growth decreases whenever DO, food availability, or energy density of available food is limiting; 2) with unlimited DO and food availability, the optimum temperature for growth increases with increasing fish size but only when energy density of food is limiting; and, 3) when neither availability nor energy density of food is limiting, growth can be much faster under diel-cycling regimes of temperature and DO than under the optimum constant temperature/DO regime. Under Ecophys.Fish, environmental regimes that are best for survival are not necessarily those that are best for growth.