Biological pesticides (i.e., biopesticides) are living systems, which introduce additional challenges with respect to formulation and delivery not previously encountered with conventional chemical pesticides. Understanding the effects of the different physical phenomena within a spray system is important to begin identifying the equipment characteristics and operating conditions that are least detrimental to the biological agents. Specifically, this work considered the effects of pressure differentials and hydrodynamic stress on damage to a benchmark biological pest control agent, entomopathogenic nematodes (EPNs). Four EPN species were evaluated in this work: Heterorhabditis bacteriophora, H. megidis, Steinernema carpocapsae, and S. glaseri. Additionally, temperature influences due to pump recirculation were investigated. Results from this work indicate that S. carpocapsae nematodes were able to withstand greater pressure differentials and more intensive hydrodynamic conditions than the other EPN species. Consequently, EPN species is an important factor to consider when defining spray operating conditions. Operating pressures within a spray system should not exceed 2000 kPa (290 psi) for H. bacteriophora and S. carpocasae, and 1380 kPa (200 psi) for H. megidis. Other EPN species may require lower pressure. Experimental results of EPN damage after passage through an abrupt contraction and two common types of hydraulic nozzles (flat fan and cone) were compared to flow parameters from numerical simulations of the experimental flow fields using FLUENT, a commercial computational fluid dynamics (CFD) program. Based on the flow field characteristics, the rotational flow regime within a cone type nozzle produces hydrodynamic conditions that are less damaging to EPNs compared to the extensional flow developed within the narrow, elliptic exit orifice of the flat fan nozzle. It was found that the tensile stress loading that occurs during flow into a constricted region, which characterizes an extensional flow, is damaging to the biological material. An empirical model comparing average energy dissipation rates computed in FLUENT to observed EPN damage was developed. Overall, the model was able to predict the EPN damage after treatment with the hydraulic nozzles well, in many cases within 5%. These results show that CFD is a feasible method to evaluate the flow conditions within an equipment component to assess its compatibility with a biological agent. Finally, extensive recirculation of the tank mix can cause considerable increases in the liquid temperature. It was found that either a diaphragm or roller pump is better suited for use with biopesticides, compared to a high-capacity centrifugal pump, which contributes significant heat to the spray system.